Cyclic ether esters of 2-substituted-6-(substituted and unsubstituted) dihydrolysergic acid useful as 5HT receptor antagonists

Abstract

Cyclic ether esters of 1-substituted-6-C 1-4 straight chain alkyl (or allyl)ergoline-8β-carboxylic acid, useful as 5HT receptor antagonists.

We claim: 
     
       1. A compound of the formula: ##STR10## wherein R is primary or secondary C 1-8  alkyl, C 2-4  alkenyl-CH 2 , C 3-8  cycloalkyl or C 3-6  cycloalkyl substituted C 1-5  primary or secondary alkyl, the total number of carbon atoms in R not to exceed 8; R 1  is allyl, H or C 1-4  straight-chain alkyl; and R 2  is ##STR11## wherein n is 0-4 and m is 1 or 2 except that, when n is 0, the ester function may not be attached to the cyclic ether ring alpha to the ring oxygen; and pharmaceutically acceptable acid addition salts thereof. 
     
     
       2. A compound according to claim 1 in which R is isopropyl. 
     
     
       3. A compound according to claim 1 in which R 1  is H. 
     
     
       4. A compound according to claim 1 in which R 1  is C 1-4  straight chain alkyl. 
     
     
       5. A compound according to claim 1 in which R 2  is 3-(2-tetrahydrofuranyl)propyl. 
     
     
       6. A compound according to claim 1 in which R 2  is 2-tetrahydropyranylmethyl. 
     
     
       7. A compound according to claim 1 in which R 2  is 2-tetrahydrofuranylmethyl. 
     
     
       8. A compound according to claim 1 in which R 2  is 4-tetrahydropyranyl. 
     
     
       9. A compound according to claim 1, said compound being 4-tetrahydropyranyl 1-isopropyl-9,10-dihydrolysergate. 
     
     
       10. A compound according to claim 1, said compound being 2-tetrahydrofuranylmethyl 1-isopropyl-9,10-dihydrolysergate. 
     
     
       11. A compound according to claim 1, said compound being 2-tetrahydropyranylmethyl 1-isopropyl-9,10-dihydrolysergate. 
     
     
       12. A compound according to claim 1, said compound being 3-(2-tetrahydrofuranyl)propyl 1-isopropyl-9,10-dihydrolysergate. 
     
     
       13. A method of blocking 5HT 2  receptors which comprises administering to a mammal having an excess of serotonin centrally or peripherally an 5HT 2  blocking dose of a compound according to claim 1. 
     
     
       14. A method of treating hypertension which comprises administering to a hypertensive mammal, a hypotensive dose of a compound according to claim 4. 
     
     
       15. A method of treating migraine which comprises administering to a mammal suffering from migraine, a migraine relieving dose of a compound according to claim 4. 
     
     
       16. A method of treating vasospasm which comprises administering to a mammal experiencing vasospasm, a vasospasm relieving dose of a compound according to claim 4. 
     
     
       17. A process according to claim 13 in which 2-tetrahydropyranylmethyl 1-isopropyl-9,10-dihydrolysergate is the drug employed. 
     
     
       18. A process according to claim 13 in which 2-tetrahydrofuranylmethyl 1-isopropyl-9,10-dihydrolysergate is the drug employed. 
     
     
       19. A process according to claim 13 in which 4-tetrahydropyranyl 1-isopropyl-9,10-dihydrolysergate is the drug employed. 
     
     
       20. A process according to claim 13 in which 3-(2-tetrahydrofuranyl)propyl 1-isopropyl-9,10-dihydrolysergate is the drug employed.